Curing of coatings through ultraviolet (UV) radiation requires efficient methods of initiating the chemical reaction responsible for the curing process. Curing of polymeric material through generation of radical species upon irradiation with UV light is widely used to produce coatings for medical devices. The paint and lacquer industry also makes use of UV-initiated curing of acrylates, where photoinitiators in many cases are employed. These two examples illustrate the diversity of UV curable coatings.
In a UV curing process, a photoinitiator moiety (low molecular weight or polymer-bound) absorbs UV light and undergoes transition to an excited state, which undergoes further processes which result in the formation of free radicals. This stage is known as initiation.
A polymer photocrosslinking process starts out with long linear polymer chains, and the initiation stage proceeds as described above. Through hydrogen abstraction, the free radicals can be transferred from the photoinitiator to an existing polymer backbone. Hereby forming new carbon-carbon bonds via radical recombination between the polymer chains providing a cross-linking of the before linear polymer chain. Such photoinitiators can be either of low molecular weight or bound in a polymer backbone.
One advantage of this photocrosslinking method is that a linear polymer has considerably different properties than the same type of polymer being cross-linked. The linear polymer may for example be soluble and can then be used in different production processes; it may be e.g. applied on medical devices by spraying or dip coating. The photocrosslinking process may then be initiated afterwards, cross-linking the polymer attaching it to the surface it is applied upon. It will neither dissolve nor melt.
Alternatively, the free radicals formed in the initiation stage may react with unsaturated monomers. This is then called a radical propagation stage. As the unsaturated moieties are transformed to new carbon-carbon bonds, the molecular weight of the radical grows and a new polymer chain is formed, i.e. the polymer is formed from unsaturated monomers and is cross-linked in the same process.
Until recently, polymers designed for use in coatings have relied on photoinitiators with relatively low molecular weight to initiate the cross-linking. Low molecular weight substances, and their by-products in the polymerization reaction, are generally difficult to remove from the resultant cross-linked polymer, but instead remain within the polymer matrix and diffuse slowly to the surface of the polymer during its lifetime. Over time, low molecular weight substances therefore leach from the polymer into the surrounding environment.
This presents particular problems in the polymers used in the medical field, as patient safety considerations limit the amount and type of substance which can leach from a given polymer. This is especially relevant if the polymer is to be used as a coating or adhesive which is designed to be in contact with the inside or outside of the patient's body.
Higher molecular weight photoinitiators, in particular polymeric photoinitiators, have comparably higher intrinsic viscosities which most likely result in longer diffusion times through a matrix. Migration of the UV active substances to the surface is therefore diminished when polymeric photoinitiators are used as opposed to lower molecular weight photoinitiators. Scarce literature within the field of polymeric photoinitiators suggests that development of such polymers could lead to novel applications and present solutions for existing needs, such as providing a material with negligent migration of substances to the surface/patient.
The majority of commercial polymeric initiators are based on a linear polymer backbone structure where a photoinitiator species is attached by a linking group to one (WO 96/33156) or both (U.S. Pat. No. 4,602,097) ends of a polymeric chain. While this type of structure provides a cost effective route to production of non-migratable photoinitiators, the linear structures tend to give rise to viscous oils and resinous materials. More problematic, the active photoinitiator weight fraction of the molecule is significantly reduced compared to the parent monomer and therefore a reduction in photoactivity by 50% or more is typically observed.
WO 2009/016083 reports a method for improving the degradation of natural or synthetic polymers by incorporating degradation accelerators into polymers composition prior to forming any products. Among the described degradation accelerators are oligomeric benzophenone compounds having amide linkers and ester bonds. It is described that such polymer products are degradable triggered by light, heat or humidity.
WO 2008/070737 relates to benzophenone and thioxanthone derivatives and their use in UV curable compositions. The examples therein show how sulphur containing benzophenone derivatives are reacted with acrylate formulations. The derivatives all have at least three ester linkers in each structure.
Polymeric photoinitiators based on a polyurethane main chain have been reported by Wei et al. (Macromolecules 2009, 42, 5486-5491). However, all materials prepared are linear polymeric structures with initiator species within the chain itself. While synthetically available, the present inventors find that ‘in-chain’ polymeric photoinitiators tend to suffer from intrinsically lower photoactivity compared to the photoinitiator monomers. Moreover, linear polymers with in-chain aromatic moieties are prone to give materials with higher degree of crystallinity and much lower solubility compared to other polymer architectures.
Accordingly, it is an object of the present invention to provide polymeric photoinitiators having better photoactivity, in order to efficiently substitute low weight photoinitiators, where migration from the final products are critical. Additionally, it is desirable that such polymeric photoinitiators have good processing properties in the linear polymer state, for use in e.g. coating processes.
It is furthermore an object of the present invention to provide photoinitiators monomers that are stable under the chemical reaction conditions used during handling and polymerisation. This in order to additionally minimise the number of degradation products and by-products that may be present in the final polymeric matrix, and hence the above described migration from the matrix.
A photoinitiator comprising a photoinitiator moiety, an ester linker and two functional groups used in polymerisation of a polyester have been described by Whitten et al. The polymers prepared are photodegraded by means of UV light with λ>340 nm. The fragmentation reaction relies on inter- or intramolecular single electron transfer (SET) between 1,2-diamine donor units and anthraquinone acceptor units followed by photooxidative C—C bond cleavage. The polymerisation reaction disclosed is a reaction between two hydroxy groups and a diacid chloride carried out in dichloroethane with hexanedioyl dichloride and pyridine base (J. Am. Chem. Soc. vol 117, No. 8, 2226-2235, 1995). WO2009016083 describes synthesis of a similar photoactive polyester from 2-benzoyl-N,N-bis(2-hydroxyethyl)benzamide and terephthaloyl chloride with triethylamine base in refluxing THF. The present inventors find that these fairly mild esterification conditions are generally not suitable for large scale industrial production of polyester polymers. This due to both high cost and toxicity of base co-reagents, such as pyridine and triethylamine, and environmental concerns regarding chlorinated solvents. Industrial production of polyesters relies on more robust, albeit slower reactions starting from e.g. diols, dicarboxylic acids, diesters or hydroxyacids, rather than expensive diacid chlorides. This requires photoinititiators compatible and stable under typical harsh transesterification conditions: Reaction temperatures in direct esterification or transesterification processes can exceed 200° C., and strong acid catalysts are used such as mineral acids, titanium alkoxides or dialkyltin oxides.
A further object of the present invention is to provide polymers with even higher backbone stability than polyesters, particularly when these are to be applied as coatings in various melt and coextrusion processes. Polyetherification reactions are typically carried out at temperatures that may exceed 150° C. in the presence of strong bases such as alkali metal hydroxides or carbonates. Reaction conditions used in such large scale polyetherification processes are generally incompatible with the presence of ester or amide linkages in the co-monomer molecules, when degradation products are to be avoided.
For example, the previously known photoinitiator molecules in which a linker with two reactive groups is tethered to a photoinitiator moiety through an ester linkage would be hydrolysed, and polyether polymers with pendant photoinitiator groups could not be obtained. For this reason, the photoinitiator diol discussed above described by Whitten et al. would not be suitable for large scale production of neither polyethers nor polyesters.
Accordingly, there has been an unmet need for photoinitiator monomers capable of being incorporated into polymeric photoinitiators in industrial scale production where costs and environmental load of toxic solvents plays a role. This is especially relevant in the production of polyethers or polyesters.
The present invention provides polymer photoinitiators in which the photoinitiator moiety itself becomes an integral part of the polymer, and remains so, during and after the polymerization process. Leaching of photoinitiator and photoinitiator by-products is therefore reduced or even eliminated. Polymers likely to improve medical safety are thereby obtained.
The photoinitiators of the present invention additionally allow for production on industrial scale under strongly acidic or strongly basic conditions which can lead to hydrolysis of moieties such as esters and amides.